Study of Non-Myeloablative Haplo-identical Haematopoietic Stem Cell Transplantation in Patients With Haematological Malignancies or Acquired Aplastic Anaemia
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Haematological Malignancies
- Sponsor
- National University Hospital, Singapore
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- 1 year overall survival after HLA-Haploidentical transplantation
- Last Updated
- 12 years ago
Overview
Brief Summary
Allogeneic haematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for patients with both haematological and some non-haematological disorders. However, one of the major limiting factors for transplantation is the inability to identify a suitable HLA-matched donor. Development of an cost-effective and clinically efficacious alternative to HLA-identical sibling or unrelated donor transplantation would significantly expand the availability of allogeneic HSCT to patients in Singapore. Preliminary results indicate that the use of high dose post-transplant cyclophosphamide (Cy) for graft versus host disease (GVHD) prophylaxis in haplo-identical allogeneic HSCT is associated a low incidence of GVHD and low treatment related toxicity. We propose a phase II clinical trial to assess the efficacy of a haplo-identical allogeneic transplantation protocol using high dose post-transplant Cy for the treatment of patients with haematological disorders. A non-myeloablative protocol (Fludarabine-low dose cyclophosphamide-TBI) will be used for patients with bone marrow failure syndromes and indolent lymphoid disease. In view of the higher relapse risk of patients with myeloid malignancies, these patients will be treated with a reduced intensity conditioning regimen (Fludarabine-Busulphan). The primary end-point of the study will be overall survival at one year. Economic cost of the haplo-identical transplantation, as well as treatment timelines will be recorded and compared will other forms of unrelated donor allogeneic transplantation (umbilical cord blood transplantation and unrelated HLA-matched adult donor). Immunological reconstitution of patients following haplo-transplantation will be analysed and data will be utilized to guide future immunotherapy strategies post-transplantation.
One year survival after non-myeloablative haploidentical stem cell transplantation is not inferior to that observed after non-myeloablative volunteer unrelated donor or unrelated cord blood haematopoietic stem cell transplantation.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient Selection Inclusion criteria
- •Age under 70 years and older than 18 years
- •Absence of HLA fully compatible related donor
- •Need for an urgent transplantation, defined as within 8 weeks of referral to the transplant centre or absence of HLA-compatible VUD after searching the international registries. Patients with a HLA-compatible VUD but whose donor is considered by the transplantation centre as unsuitable will also be eligible.
- •Informed consent.
- •Disease inclusion criteria:
- •In general this encompasses all haematological disorders where a volunteer unrelated donor (UD) transplant is clinically indicated.
- •Acute, chronic leukaemia or myelodysplastic syndrome for which allogeneic transplantation is considered as the best treatment option.
- •a. Acute myeloid leukaemia (AML) i. In first complete remission (CR1) with one of the following characteristics:
- •High risk cytogenetic or molecular alterations (e.g. t(9;22), deletion 7/7q-, monosomy 5 or del(5q), 3q26 alterations, complex karyotype \[3 or more anomalies\], p53 alterations, 11q23 especially t(6;11) abnormalities, FLT-3 ITD, monosomal karyotype.
Exclusion Criteria
- •Patients with an available 7-8/8 HLA-A, -B, -C, -DRB1 matched sibling donor or 7-8/8 unrelated bone marrow donor
- •Availability of suitable UCB unit/s and eligible for an UCB transplant
- •ECOG performance status worse than 2
- •Cardiac insufficiency requiring treatment, symptomatic coronary artery disease or LVEF less than 35%.
- •Hepatic disease, with total bilirubin greater than 2 times upper limit of normal or AST \> 5 times upper limit of normal.
- •Severe hypoxaemia, pO2 \< 70 mm Hg, with decreased DLCO \< 50% of predicted; or mild hypoxemia, pO2 \< 80 mm Hg with severely decreased DLCO \< 50% of predicted.
- •Impaired renal function (creatinine \> 2 times upper limit of normal or creatinine clearance \< 50% for age, gender, weight).
- •Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI).
- •HIV positive patients.
- •Female patients who are pregnant or breast feeding due to risks to foetus from conditioning regimen and potential risks to nursing infants.
Outcomes
Primary Outcomes
1 year overall survival after HLA-Haploidentical transplantation
Time Frame: 1 year
Secondary Outcomes
- Progression free survival one and 2 years post-transplantation(2 years)
- Cumulative incidence of relapse/progression at one and 2 years post-transplant(2 years)